CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn's Disease

Background and Aims: Tumour necrosis factor [TNF]alpha- and IL-17A-producing T cells are implicated in Crohn's disease [CD]. Tissue-resident memory T [T-RM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic T-h 17 cell responses. T-RM cells provide host defence but their role in CD is unknown. We thus examined CD4(+) T-RM cells in CD. Methods: Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4(+) T-RM cells. Results: CD4(+) T-RM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNF alpha in CD. CD4(+) T-RM cells are expanded in CD and more avidly produce IL-17A and TNF alpha relative to control cells. There was a unique population of TNF alpha+IL-17A(+) CD4(+) T-RM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4(+) T-RM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4(+) T-RM cells Conclusions: CD4(+) T-RM cells are expanded in CD and are a major source of TNF alpha, suggesting that they are important in CD. PRDM1 is expressed by T-RM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4(+) T-RM cells over the disease course.